Major depression (MDD) is a common and potentially devastating illness which likely has many etiologies, environmental as well as genetic. Unfortunately, biochemical and physiological experiments have so far failed to provide unequivocal, objective diagnostic markers for the illness, or to delineate specific pathological processes that are rectified by pharmacological treatments. Genetic approaches may only partially elucidate the neurobiology of depression, but the discovery of even one rare MDD predisposing gene will help guide efforts to understand mood disorders in general. Obstacles to identifying genes for psychiatric disorders include the lack of objective criteria for defining the disease phenotype and extensive etiologic heterogeneity. However, recent technological advances in molecular genetics have facilitated processing of the large samples required to find genes of small effect. As well, it is now generally recognized that genetic heterogeneity can be reduced by defining only the most severe form of a particular phenotype as affected and, possibly, by studying genetically isolated populations. Thus, the candidate intends to identify genes predisposing to mood disorder by applying population genetic mapping methods to study subjects with early onset recurrent MDD collected from an isolated population in the Central Valley of Costa Rica. The candidate is a postdoctoral fellow in psychiatry and has spent the last three years investigating the genetics of bipolar disorder in the laboratory of Nelson Freimer MD at UCSF. Short term career goals are to remain in this laboratory as an adjunct assistant professor, to further develop her knowledge of statistical approaches to the genetics of complex traits and to characterize the phenotypes associated with the genes she discovers for mood disorders. The latter endeavor will aid and be aided by 20 percent time clinical work related to affective disorders. The candidate's long-term goal is to establish an independent academic career continuing her genetic investigation of psychiatric disorders. It is hoped this work will ultimately lead to better patient care, the revision of psychiatric nosology in terms of etiology rather than symptoms, and the elimination of some of the stigma that surrounds mental illness that persists, in part, because of our inability to characterize the biology of complex behaviors.